Hiperplasia endometrial II: Revisión narrativa sobre diferentes opciones de tratamiento.
Endometrial hyperplasia II: A narrative review of different treatment options.
Palabras clave:
Hiperplasia Endometrial, Tratamiento Conservador, Terapia Hormonal, Progestágenos, Tratamiento Quirúrgico
Resumen
La hiperplasia endometrial comprende un espectro de cambios en el endometrio que van desde un patrón ligeramente desordenado, como la hiperplasia endometrial sin atipias, hasta alteraciones más severas, como la hiperplasia endometrial con atipias, precursora del carcinoma endometrial. Durante los años reproductivos, el riesgo de la hiperplasia está asociado a oligo-anovulación, y durante la menopausia está asociado con factores como la obesidad y la terapia de reemplazo de estrógeno. Esta revisión tiene por objeto, ofrecer un enfoque racional en el tratamiento de la hiperplasia endometrial, incluidos la terapia conservadora como la hormonal y los diferentes métodos quirúrgicos.
Descargas
La descarga de datos todavía no está disponible.
Citas
Montgomery BE, Daum GS, Dunton CJ. Endometrial hyperplasia: a review. Obstet Gynecol Surv. 2004; 59(5):368-378. https://doi.org/10.1097/00006254-200405000-00025.
Höhn AK, Brambs CE, Hiller GGR, May D, Schmoeckel E, Horn LC. 2020 WHO Classification of Female Genital Tumors. Geburtshilfe Frauenheilkd. 2021; 81(10):1145-1153. https://doi.org/10.1055/a-1545-4279.
Ring KL, Mills AM, Modesitt SC. Endometrial Hyperplasia. Obstet Gynecol. 2022;140(6):1061-1075. https://doi.org/10.1097/AOG.0000000000004989.
Sobczuk K, Sobczuk A. New classification system of endometrial hyperplasia WHO 2014 and its clinical implications. Prz Menopauzalny. 2017; 16(3):107-111. https://doi.org/10.5114/pm.2017.70589.
Ricci E, Moroni S, Parazzini F, Surace M, Benzi G, Salerio B, et al. Risk factors for endometrial hyperplasia: results from a case-control study. Int J Gynecol Cancer. 2002; 12(3):257-260. https://doi.org/10.1046/j.1525-1438.2002.01105.x.
Chandra V, Kim JJ, Benbrook DM, Dwivedi A, Rai R. Therapeutic options for management of endometrial hyperplasia. J Gynecol Oncol. 2016; 27(1):e8. https://doi.org/10.3802/jgo.2016.27.e8.
Armstrong AJ, Hurd WW, Elguero S, Barker NM, Zanotti KM. Diagnosis and management of endometrial hyperplasia. J Minim Invasive Gynecol. 2012; 19(5):562-571. https://doi.org/10.1016/j.jmig.2012.05.009.
Reed SD, Newton KM, Clinton WL, Epplein M, Garcia R, Allison K, et al. Incidence of endometrial hyperplasia. Am J Obstet Gynecol. 2009; 200(6):678. e1-6. https://doi.org/10.1016/j.ajog.2009.02.032.
Natarajan P, Vinturache A, Hutson R, Nugent D, Broadhead T. The value of MRI in management of endometrial hyperplasia with atypia. World J Surg Oncol. 2020; 18(1):34. https://doi.org/10.1186/s12957-020-1811-5.
Whitaker L, Critchley HO. Abnormal uterine bleeding. Best Pract Res Clin Obstet Gynaecol. 2016; 34:54-65. https://doi.org/10.1016/j.bpobgyn.2015.11.012.
International Agency for Cancer Re-search. World Health Organization. The Global Cancer Observatory (GCO). Corpus uteri. Cancer Today. 2020. Disponible en: https://gco.iarc.who.int/media/globocan/factsheets/cancers/24-corpus-uteri-fact-sheet.pdf.
Siegel RL, Miller KD, Wagle NS, Jemal Cancer statistics, 2023. CA Cancer J Clin. 2023; 73(1):17-48. https://doi.org/10.3322/caac.21763.
National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer stat facts: uterine cancer. 2023. Disponible en: https://seer.cancer.gov/statfacts/html/cervix.html.
Coulam CB, Annegers JF, Kranz JS. Chronic anovulation syndrome and associated neoplasia. Obstet Gynecol. 1983; 61(4):403-407. PMID: 6828267.
Göl K, Saraçoğlu F, Ekici A, Sahin I. Endometrial patterns and endocrinologic characteristics of asymptomatic menopausal women. Gynecol Endocrinol. 2001; 15(1):63-67. PMID: 11293927.
Martínez-Núñez EN, Carvallo-Ruiz DE, Núñez-Troconis JT. Gynecological uses of GnRH antagonists: review article. Obstet Gynecol Int J. 2022; 13(4):226-238. https://doi.org/10.15406/ogij.2022.13.00654.
Scully RE, Bonfiglio TA, Kurman RJ, Silverberg SG, Wilkinson EJ. International Histological Classification and Typing of Female Genital Tract Tumours. 2nd Ed. New York, NY: Springer-Verlag; 1994: 1–189. https://doi.org/10.1007/978-3-642-85014-1.
Baak JP, Mutter GL, Robboy S, van Diest PJ, Uyterlinde AM, Orbo A, et al. The molecular genetics and morphometry-based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 World Health Organization classification system. Cancer. 2005;103(11):2304-2312. https://doi.org/10.1002/cncr.21058.
Auclair MH, Yong PJ, Salvador S, Thurston J, Colgan TTJ, Sebastianelli A. Guideline No. 390-Classification and Management of Endometrial Hyperplasia. J Obstet Gynaecol Can. 2019; 41(12):1789-1800. https://doi.org/10.1016/j.jogc.2019.03.025. Erratum in: J Obstet Gynaecol Can. 2020; 42(10):1287.
Jewson M, Purohit P, Lumsden MA. Progesterone and abnormal uterine bleeding/ menstrual disorders. Best Pract Res Clin Obstet Gynaecol. 2020; 69:62-73. https://doi.org/10.1016/j.bpobgyn.2020.05.004.
Amezcua CA, Lu JJ, Felix JC, Stanczyk FZ, Zheng W. Apoptosis may be an early event of progestin therapy for endometrial hyperplasia. Gynecol Oncol. 2000; 79(2):169-176. https://doi.org/10.1006/gyno.2000.5955.
Abulafia O, Triest WE, Adcock JT, Sherer DM. The effect of medroxyprogesterone acetate on angiogenesis in complex endometrial hyperplasia. Gynecol Oncol. 1999;72(2):193-198. https://doi.org/10.1006/gyno.1998.5106.
Figueroa-Casas PR, Ettinger B, Delgado E, Javkin A, Vieder C. Reversal by medical treatment of endometrial hyperplasia caused by estrogen replacement therapy. Menopause. 2001; 8(6):420-423. https://doi.org/10.1097/00042192-200111000-00006.
Reed SD, Voigt LF, Newton KM, Garcia RH, Allison HK, Epplein M, et al. Progestin therapy of complex endometrial hyperplasia with and without atypia. Obstet Gynecol. 2009; 113(3):655-662. https://doi.org/10.1097/AOG.0b013e318198a10a.
Gunderson CC, Fader AN, Carson KA, Bristow RE. Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: a systematic review. Gynecol Oncol. 2012; 125(2):477-482. https://doi.org/10.1016/j.ygyno.2012.01.003.
Brun JL, Belaisch J, Rivel J, Hocké C. Les hyperplasies endométriales résistant aux progestatifs: alternatives aux traitements traditionnels. [Endometrial hyperplasias resistant to progestins: alternatives to traditional treatments]. Gynecol Obstet Fertil. 2002; 30(3):244-251. https://doi.org/10.1016/s1297-9589(02)00301-6.
Upson K, Allison KH, Reed SD, Jordan CD, Newton KM, Swisher EM, et al. Bio-markers of progestin therapy resistance and endometrial hyperplasia progression. Am J Obstet Gynecol. 2012; 207(1):36.e1-8. https://doi.org/10.1016/j.ajog.2012.05.012.
Wang S, Pudney J, Song J, Mor G, Schwartz PE, Zheng W. Mechanisms involved in the evolution of progestin resistance in human endometrial hyperplasia--precursor of endometrial cancer. Gynecol Oncol. 2003; 88(2):108-117. https://doi.org/10.1016/s0090-8258(02)00008-2.
Chen X, Zhang Z, Feng Y, Fadare O, Wang J, Ai Z, et al. Aberrant survivin expression in endometrial hyperplasia: another mechanism of progestin resistance. Mod Pathol. 2009; 22(5):699-708. https://doi.org/10.1038/modpathol.2009.25.
van Hylckama Vlieg A, Helmerhorst FM, Rosendaal FR. The risk of deep venous thrombosis associated with injectable depot-medroxyprogesterone acetate contraceptives or a levonorgestrel intrauterine device. Arterioscler Thromb Vasc Biol. 2010; 30(11):2297-2300. https://doi.org/10.1161/ATVBAHA.110.211482.
Vasilakis C, Jick H, del Mar Melero-Montes M. Risk of idiopathic venous thromboembolism in users of progestagens alone. Lancet. 1999; 354(9190):1610-1611. https://doi.org/10.1016/S0140-6736(99)04394-9.
Heinemann LA, Assmann A, DoMinh T, Garbe E. Oral progestogen-only contraceptives and cardiovascular risk: results from the Transnational Study on Oral Contraceptives and the Health of Young Women. Eur J Contracept Reprod Health Care. 1999; 4(2):67-73. https://doi.org/10.3109/13625189909064007.
Eichner E, Abellera M. Endometrial hyperplasia treated by progestins. Obstet Gynecol. 1971; 38 (5):739-42. PMID: 5114224.
Bese T, Vural A, Ozturk M, Dagistanli F, Demirkiran F, Tuncdemir M, et al. The effect of long-term use of progesterone therapy on proliferation and apoptosis in simple endometrial hyperplasia without atypia. Int J Gynecol Cancer. 2006; 16(2):809-813. https://doi.org/10.1111/j.1525-1438.2006.00533.x.
Buttini MJ, Jordan SJ, Webb PM. The effect of the levonorgestrel releasing intrauterine system on endometrial hyperplasia: An Australian study and systematic review. Aust N Z J Obstet Gynaecol. 2009; 49(3):316-322. https://doi.org/10.1111/j.1479-828X.2009.00981.x.
Ozdegirmenci O, Kayikcioglu F, Bozkurt U, Akgul MA, Haberal A. Comparison of the efficacy of three progestins in the treatment of simple endometrial hyperplasia without atypia. Gynecol Obstet Invest. 2011; 72(1):10-14. https://doi.org/10.1159/000321390.
Ushijima K, Yahata H, Yoshikawa H, Konishi I, Yasugi T, Saito T, et al. Multi-center phase II study of fertility-sparing treatment with medroxyprogesterone acetate for endometrial carcinoma and atypical hyperplasia in young women. J Clin Oncol. 2007; 25(19):2798-2803. https://doi.org/10.1200/JCO.2006.08.8344.
Güven M, Dikmen Y, Terek MC, Ozsaran AA, Itil IM, Erhan Y. Metabolic effects associated with high-dose continuous megestrol acetate administration in the treatment of endometrial pathology. Arch Gynecol Obstet. 2001; 265(4):183-186. https://doi.org/10.1007/s004040000154.
Gal D, Edman CD, Vellios F, Forney JP. Long-term effect of megestrol acetate in the treatment of endometrial hyperplasia. Am J Obstet Gynecol. 1983; 146(3):316-322. https://doi.org/10.1016/0002-9378(83)90754-8.
Garza-Flores J, Menjívar M, Cardenas M, Reynoso M, García GA, Pérez Palacios G. Further studies on the antigonadotropic mechanism of action of norethisterone. J Steroid Biochem Mol Biol. 1991; 38(1):89-93. https://doi.org/10.1016/0960-0760(91)90406-u.
Portman DJ, Symons JP, Wilborn W, Kempfert NJ. A randomized, double-blind, placebo-controlled, multicenter study that assessed the endometrial effects of norethindrone acetate plus ethinyl estradiol versus ethinyl estradiol alone. Am J Obstet Gynecol. 2003;188(2):334-342. https://doi.org/10.1067/mob.2003.91.
Nisker JA, Kirk ME, Nunez-Troconis JT. Reduced incidence of rabbit endometrial neoplasia with levonorgestrel implant. Am J Obstet Gynecol. 1988;158(2):300-303. https://doi.org/10.1016/0002-9378(88)90142-1.
Nilsson CG, Haukkamaa M, Vierola H, Luukkainen T. Tissue concentrations of levonorgestrel in women using a levonorgestrel-releasing IUD. Clin Endocrinol (Oxf). 1982; 17(6):529-536. https://doi.org/10.1111/j.1365-2265.1982.tb01625.x.
Suhonen SP, Allonen HO, Lähteenmäki P. Sustained-release estradiol implants and a levonorgestrel-releasing intrauterine device in hormone replacement therapy. Am Obstet Gynecol. 1995; 172(2 Pt 1):562-567. https://doi.org/10.1016/0002-9378(95)90573-1.
Abu Hashim H, Zayed A, Ghayaty E, El Rakhawy M. LNG-IUS treatment of non-atypical endometrial hyperplasia in perimenopausal women: a randomized controlled trial. J Gynecol Oncol. 2013; 24(2):128-134. https://doi.org/10.3802/jgo.2013.24.2.128.
Varma R, Soneja H, Bhatia K, Ganesan R, Rollason T, Clark TJ, Gupta JK. The effectiveness of a levonorgestrel-releasing intra-uterine system (LNG-IUS) in the treatment of endometrial hyperplasia a long-term follow-up study. Eur J Obstet Gynecol Re-prod Biol. 2008; 139(2):169-175. https://doi.org/10.1016/j.ejogrb.2008.02.022.
Vereide AB, Arnes M, Straume B, Maltau JM, Ørbo A. Nuclear morphometric changes and therapy monitoring in patients with endometrial hyperplasia: a study comparing effects of intrauterine levonorgestrel and systemic medroxyprogesterone. Gynecol Oncol. 2003; 91(3):526-533. https://doi.org/10.1016/j.ygyno.2003.07.002.
Singh G, Cue L, Puckett Y. Endometrial Hyperplasia. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.
The American College of Obstetricians and Gynecologists (ACOG). Management of Endometrial Intraepithelial Neoplasia or Atypical Endometrial Hyperplasia: ACOG Clinical Consensus No. 5. Obstet Gynecol. 2023; 142(3):735-744. https://doi.org/10.1097/AOG.0000000000005297.
Gallos ID, Shehmar M, Thangaratinam S, Papapostolou TK, Coomarasamy A, Gupta JK. Oral progestogens vs levonorgestrel releasing intrauterine system for endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol. 2010; 203(6):547.e1-10. https://doi.org/10.1016/j.ajog.2010.07.037.
Greenblatt RB, Dmowski WP, Mahesh VB, Scholer HF. Clinical studies with an antigonadotropin-Danazol. Fertil Steril. 1971; 22(2):102-112. https://doi.org/10.1016/s0015-0282(16)38045-1.
Crosignani P, Olive D, Bergqvist A, Luciano A. Advances in the management of endometriosis: an update for clinicians. Hum Reprod Update. 2006; 12(2):179-189. https://doi.org/10.1093/humupd/dmi049.
Mariani L, Sedati A, Giovinazzi R, Sindico R, Atlante G. Postmenopausal endome- trial hyperplasia: role of danazol therapy. Int J Gynaecol Obstet. 1994; 44(2):155-159. https://doi.org/10.1016/0020-7292(94)90071-x.
Soh E, Sato K. Clinical effects of danazol on endometrial hyperplasia in menopausal and postmenopausal women. Cancer. 1990; 66(5):983-988. https://doi.org/10.1002/1097-0142(19900901)66:5<983:aid-cncr2820660530>3.0.co;2-6.
Grio R, Piacentino R, Marchino GL, Bocci A, Navone R. Danazol in the treatment of endometrial hyperplasia. Panminerva Med. 1993; 35(4):231-233. PMID: 8202337.
Tamaoka Y, Orikasa H, Sumi Y, Sakakura K, Kamei K, Nagatani M, Ezawa S. Treatment of endometrial hyperplasia with a danazol-releasing intrauterine device: a prospective study. Gynecol Obstet Invest. 2004; 58(1):42-48. https://doi.org/10.1159/000077882.
Cottreau CM, Ness RB, Modugno F, Allen GO, Goodman MT. Endometriosis and its treatment with danazol or lupron in relation to ovarian cancer. Clin Cancer Res. 2003; 9(14):5142-5144. PMID: 14613992.
Vercellini P, Somigliana E, Viganò P, Abbiati A, Barbara G, Crosignani PG. Endometriosis: current therapies and new pharmacological developments. Drugs. 2009; 69(6):649-675. https://doi.org/10.2165/00003495-200969060-00002.
Akiyama T, Ishida J, Nakagawa S, Ogawara H, Watanabe S, Itoh N, et al. Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem. 1987; 262(12):5592-5595. PMID: 3106339.
Yamashita Y, Kawada S, Nakano H. Induction of mammalian topoisomerase II dependent DNA cleavage by nonintercalative flavonoids, genistein and orobol. Biochem Pharmacol. 1990; 39(4):737-744. https://doi.org/10.1016/0006-2952(90)90153-c.
Lian Z, Niwa K, Tagami K, Hashimoto M, Gao J, Yokoyama Y, Mori H, Tamaya T. Preventive effects of isoflavones, genistein and daidzein, on estradiol-17beta-related endometrial carcinogenesis in mice. J Cancer Res. 2001; 92(7):726-734. https://doi.org/10.1111/j.1349-7006.2001.tb01154.x.
Bitto A, Granese R, Triolo O, Villari D, Maisano D, Giordano D, et al. Genistein aglycone: a new therapeutic approach to reduce endometrial hyperplasia. Phytomedicine. 2010; 17(11):844-850. https://doi.org/10.1016/j.phymed.2010.03.024.
Núñez-Troconis, J. Uso de la metformina en el síndrome de ovarios poliquísticos. Gac Méd Caracas. 2021;129(1):128-139. https://doi.org/10.47307/GMC.2021.129.1.14
Shao R, Li X, Feng Y, Lin JF, Billig H. Direct effects of metformin in the endometrium: a hypothetical mechanism for the treatment of women with PCOS and endometrial carcinoma. J Exp Clin Cancer Res. 2014;33(1):41. https://doi.org/10.1186/1756-9966-33-41.
Núñez-Troconis, J. Uso de la metformina en cáncer ginecológico. Gac Méd Ca- racas 2021;129(1):88-106. https://doi.org/10.47307/GMC.2021.129.1.12.
Xie Y, Wang YL, Yu L, Hu Q, Ji L, Zhang Y, Liao QP. Metformin promotes progesterone receptor expression via inhibition of mammalian target of rapamycin (mTOR) in endometrial cancer cells. J Steroid Biochem Mol Biol. 2011; 126(3-5):113-120. https://doi.org/10.1016/j.jsbmb.2010.12.006.
Erdemoglu E, Güney M, Giray SG, Take G, Mungan T. Effects of metformin on mammalian target of rapamycin in a mouse model of endometrial hyperplasia. Eur J Obstet Gynecol Reprod Biol. 2009; 145(2):195-199. https://doi.org/10.1016/j.ejogrb.2009.04.034.
Session DR, Kalli KR, Tummon IS, Damario MA, Dumesic DA. Treatment of atypical endometrial hyperplasia with an insulin-sensitizing agent. Gynecol Endocrinol. 2003; 17(5):405-407. https://doi.org/10.1080/09513590312331290298.
Shen ZQ, Zhu HT, Lin JF. Reverse of progestin-resistant atypical endometrial hyperplasia by metformin and oral contraceptives. Obstet Gynecol. 2008;112(2 Pt 2):465-467. https://doi.org/10.1097/AOG.0b013e3181719b92.
Meresman GF, Bilotas MA, Lombardi E, Tesone M, Sueldo C, Barañao RI. Effect of GnRH analogues on apoptosis and release of interleukin-1beta and vascular endothelial growth factor in endometrial cell cultures from patients with endometriosis. Hum Reprod. 2003; 18(9):1767-1771. https://doi.org/10.1093/humrep/deg356.
Fister S, Günthert AR, Emons G, Gründker C. Gonadotropin-releasing hormone type II antagonists induce apoptotic cell death in human endometrial and ovarian cancer cells in vitro and in vivo. Cancer Res. 2007; 67(4):1750-1756. https://doi.org/10.1158/0008-5472.CAN-06-3222.
Agorastos T, Bontis J, Vakiani A, Vavilis D, Constantinidis T. Treatment of endometrial hyperplasias with gonadotropin-releasing hormone agonists: pathological, clinical, morphometric, and DNA-cytometric data. Gynecol Oncol. 1997; 65(1):102-114. https://doi.org/10.1006/gyno.1997.4639.
Agorastos T, Vaitsi V, Paschopoulos M, Vakiani A, Zournatzi-Koiou V, Saravelos H, et al. Prolonged use of gonadotropin releasing hormone agonist and tibolone as add-back therapy for the treatment of endometrial hyperplasia. Maturitas. 2004;48(2):125-132. https://doi.org/10.1016/j.maturitas.2003.08.008.
Yu K, Huang ZY, Xu XL, Li J, Fu XW, Deng SL. Estrogen Receptor Function: Impact on the Human Endometrium. Front Endocrinol (Lausanne). 2022; 13:827724. https://doi.org/10.3389/fendo.2022.827724.
Long BJ, Tilghman SL, Yue W, Thiantanawat A, Grigoryev DN, Brodie AM. The steroidal antiestrogen ICI 182,780 is an inhibitor of cellular aromatase activity. J Steroid Biochem Mol Biol. 1998; 67(4):293-304. https://doi.org/10.1016/s0960-0760(98)00122-8.
Scott SM, Brown M, Come SE. Emerging data on the efficacy and safety of Fulvestrant, a unique antiestrogen therapy for advanced breast cancer. Expert Opin Drug Saf. 2011; 10(5):819-826. https://doi.org/10.1517/14740338.2011.595560.
Sourla A, Luo S, Labrie C, Bélanger A, Labrie F. Morphological changes induced by 6-month treatment of intact and ovariectomized mice with tamoxifen and the pure antiestrogen EM-800. Endocrinology. 1997; 138(12):5605-5617. https://doi.org/10.1210/endo.138.12.5560.
Tremblay A, Tremblay GB, Labrie C, Labrie F, Giguère V. EM-800, a novel antiestrogen, acts as a pure antagonist of the transcriptional functions of estrogen receptors alpha and beta. Endocrinology. 1998; 139(1):111-118. https://doi.org/10.1210/endo.139.1.5702.
Fatima I, Chandra V, Saxena R, Manohar M, Sanghani Y, Hajela K, et al. 2,3-Diaryl-2H-1-benzopyran derivatives interfere with classical and non-classical estrogen receptor signaling pathways, inhibit Akt activation and induce apoptosis in human endometrial cancer cells. Mol Cell Endocrinol. 2012; 348(1):198-210. https://doi.org/10.1016/j.mce.2011.08.018.
Chandra V, Fatima I, Saxena R, Kitchlu S, Sharma S, Hussain MK, et al. Apoptosis induction and inhibition of hyperplasia formation by 2-[piperidinoethoxyphenyl]- 3-[4-hydroxyphenyl]-2H-benzo(b)pyran in rat uterus. Am J Obstet Gynecol. 2011; 205(4):362.e1-11. https://doi.org/10.1016/j.ajog.2011.05.024. Erratum in: Am J Obstet Gynecol. 2020; 222(1):84.
Chandra V, Fatima I, Manohar M, Popli P, Sirohi VK, Hussain MK, et al. Inhibitory effect of 2-(piperidinoethoxyphenyl)-3-(4-hydroxyphenyl)-2H-benzo(b)pyran (K-1) on human primary endometrial hyperplasial cells mediated via combined suppression of Wnt/β-catenin signaling and PI3K/ Akt survival pathway. Cell Death Dis. 2014; 5(8):e1380. https://doi.org/10.1038/cddis.2014.334.
Fabian CJ. The what, why and how of aromatase inhibitors: hormonal agents for treatment and prevention of breast cancer. Int J Clin Pract. 2007; 61(12):2051- 2063. https://doi.org/10.1111/j.1742-1241.2007.01587.x.
Bershteĭn LM, Maksimov SIa, Danilova MA, Gershfel’d ÉD, Boiarkina MP, Khadzhimba AS, et al. [Effectiveness of aromatase inhibitors in comparison with metformin for neoadjuvant treatment in patients with endometrial cancer]. Vopr Onkol. 2011; 57(6):737-741. Russian.PMID: 22416390.
Lai CH, Huang HJ. The role of hormones for the treatment of endometrial hyperplasia and endometrial cancer. Curr Opin Obstet Gynecol. 2006; 18(1):29-34. https://doi.org/10.1097/01.gco.0000192994.37965.c6.
Barker LC, Brand IR, Crawford SM. Sustained effect of the aromatase inhibitors anastrozole and letrozole on endometrial thickness in patients with endometrial hyperplasia and endometrial carcinoma. Curr Med Res Opin. 2009; 25(5):1105-1109. https://doi.org/10.1185/03007990902860549.
Tabatabaie A, Karimi Zarchi M, Dehghani-Tafti M, Miratashi-Yazdi A, Teimoori S, Dehghani A. Comparing letrozole with medroxyprogesterone acetate (MPA) as hormonal therapy for simple endometrial hyperplasia without atypia in adult and middle-aged women. Eur J Gynaecol Oncol. 2013; 34(6):552-555. PMID:24601050.
El-shamy M, Gibreel A, Refai E, Sadek E, Ragab A. Aromatase inhibitor “letrozole” versus progestin “norethisterone” in women with simple endometrial hyperplasia without atypia: a prospective co-hort trial. Middle East Fertil Soc J. 2012; 17(2):111-115. https://doi.org/10.1016/j.mefs.2011.11.005.
Agorastos T, Vaitsi V, Pantazis K, Efstathiadis E, Vavilis D, Bontis JN. Aromatase inhibitor anastrozole for treating endometrial hyperplasia in obese postmenopausal women. Eur J Obstet Gynecol Re-prod Biol. 2005; 118(2):239-240. https://doi.org/10.1016/j.ejogrb.2004.07.002.
Guo Y, Chen Y, Liu LB, Chang KK, Li H, Li MQ, Shao J. IL -22 in the endometriotic milieu promotes the proliferation of endometrial stromal cells via stimulating the secretion of CCL2 and IL-8. Int J Clin Exp Pathol. 2013; 6(10):2011-2020. PMID:2133578.
Bruchim I, Sarfstein R, Werner H. The IGF Hormonal Network in Endometrial Cancer: Functions, Regulation, and Targeting Approaches. Front Endocrinol (Lausanne). 2014; 5:76. https://doi.org/10.3389/fendo.2014.00076.
Li MQ, Li HP, Meng YH, Wang XQ, Zhu XY, Mei J, Li DJ. Chemokine CCL2 enhances survival and invasiveness of endometrial stromal cells in an autocrine manner by activating Akt and MAPK/Erk1/2 signal pathway. Fertil Steril. 2012; 97(4):919-929. https://doi.org/10.1016/j.fertnstert.2011.12.049.
Del Priore G, Gudipudi DK, Montemarano N, Restivo AM, Malanowska-Stega J, Arslan AA. Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia. Gynecol Oncol. 2010;116(3):464-467. https://doi.org/10.1016/j.ygyno.2009.10.060.
Dalessandri KM, Firestone GL, Fitch MD, Bradlow HL, Bjeldanes LF. Pilot study: effect of 3,3’-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutr Cancer. 2004;50(2):161-167. https://doi.org/10.1207/s15327914nc5002_5.
Chen DZ, Qi M, Auborn KJ, Carter TH. Indole-3-carbinol and diindolylmethane induce apoptosis of human cervical cancer cells and in murine HPV16-transgenic preneoplastic cervical epithelium. J Nutr. 2001;131(12):3294-3302. https://doi.org/10.1093/jn/131.12.3294.
Savino JA 3rd, Evans JF, Rabinowitz D, Auborn KJ, Carter TH. Multiple, disparate roles for calcium signaling in apoptosis of human prostate and cervical cancer cells exposed to diindolylmethane. Mol Cancer Ther. 2006;5(3):556-563. https://doi.org/10.1158/1535-7163.MCT-05-0355.
Leong H, Firestone GL, Bjeldanes LF. Cytostatic effects of 3,3′-diindolylmethane in human endometrial cancer cells result from an estrogen receptor-mediated increase in transforming growth factor-α expression. Carcinogenesis. 2001; 22(11):1809-1817. https://doi.org/10.1093/carcin/22.11.1809.
Järvelä I, Tekay A, Santala M, Jouppila P. Thermal balloon endometrial ablation therapy induces a rise in uterine blood flow impedance: a randomized prospective color Doppler study. Ultrasound Obstet Gynecol. 2001;17(1):65-70. https://doi.org/10.1046/j.1469-0705.2001.00317.
Höhn AK, Brambs CE, Hiller GGR, May D, Schmoeckel E, Horn LC. 2020 WHO Classification of Female Genital Tumors. Geburtshilfe Frauenheilkd. 2021; 81(10):1145-1153. https://doi.org/10.1055/a-1545-4279.
Ring KL, Mills AM, Modesitt SC. Endometrial Hyperplasia. Obstet Gynecol. 2022;140(6):1061-1075. https://doi.org/10.1097/AOG.0000000000004989.
Sobczuk K, Sobczuk A. New classification system of endometrial hyperplasia WHO 2014 and its clinical implications. Prz Menopauzalny. 2017; 16(3):107-111. https://doi.org/10.5114/pm.2017.70589.
Ricci E, Moroni S, Parazzini F, Surace M, Benzi G, Salerio B, et al. Risk factors for endometrial hyperplasia: results from a case-control study. Int J Gynecol Cancer. 2002; 12(3):257-260. https://doi.org/10.1046/j.1525-1438.2002.01105.x.
Chandra V, Kim JJ, Benbrook DM, Dwivedi A, Rai R. Therapeutic options for management of endometrial hyperplasia. J Gynecol Oncol. 2016; 27(1):e8. https://doi.org/10.3802/jgo.2016.27.e8.
Armstrong AJ, Hurd WW, Elguero S, Barker NM, Zanotti KM. Diagnosis and management of endometrial hyperplasia. J Minim Invasive Gynecol. 2012; 19(5):562-571. https://doi.org/10.1016/j.jmig.2012.05.009.
Reed SD, Newton KM, Clinton WL, Epplein M, Garcia R, Allison K, et al. Incidence of endometrial hyperplasia. Am J Obstet Gynecol. 2009; 200(6):678. e1-6. https://doi.org/10.1016/j.ajog.2009.02.032.
Natarajan P, Vinturache A, Hutson R, Nugent D, Broadhead T. The value of MRI in management of endometrial hyperplasia with atypia. World J Surg Oncol. 2020; 18(1):34. https://doi.org/10.1186/s12957-020-1811-5.
Whitaker L, Critchley HO. Abnormal uterine bleeding. Best Pract Res Clin Obstet Gynaecol. 2016; 34:54-65. https://doi.org/10.1016/j.bpobgyn.2015.11.012.
International Agency for Cancer Re-search. World Health Organization. The Global Cancer Observatory (GCO). Corpus uteri. Cancer Today. 2020. Disponible en: https://gco.iarc.who.int/media/globocan/factsheets/cancers/24-corpus-uteri-fact-sheet.pdf.
Siegel RL, Miller KD, Wagle NS, Jemal Cancer statistics, 2023. CA Cancer J Clin. 2023; 73(1):17-48. https://doi.org/10.3322/caac.21763.
National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer stat facts: uterine cancer. 2023. Disponible en: https://seer.cancer.gov/statfacts/html/cervix.html.
Coulam CB, Annegers JF, Kranz JS. Chronic anovulation syndrome and associated neoplasia. Obstet Gynecol. 1983; 61(4):403-407. PMID: 6828267.
Göl K, Saraçoğlu F, Ekici A, Sahin I. Endometrial patterns and endocrinologic characteristics of asymptomatic menopausal women. Gynecol Endocrinol. 2001; 15(1):63-67. PMID: 11293927.
Martínez-Núñez EN, Carvallo-Ruiz DE, Núñez-Troconis JT. Gynecological uses of GnRH antagonists: review article. Obstet Gynecol Int J. 2022; 13(4):226-238. https://doi.org/10.15406/ogij.2022.13.00654.
Scully RE, Bonfiglio TA, Kurman RJ, Silverberg SG, Wilkinson EJ. International Histological Classification and Typing of Female Genital Tract Tumours. 2nd Ed. New York, NY: Springer-Verlag; 1994: 1–189. https://doi.org/10.1007/978-3-642-85014-1.
Baak JP, Mutter GL, Robboy S, van Diest PJ, Uyterlinde AM, Orbo A, et al. The molecular genetics and morphometry-based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 World Health Organization classification system. Cancer. 2005;103(11):2304-2312. https://doi.org/10.1002/cncr.21058.
Auclair MH, Yong PJ, Salvador S, Thurston J, Colgan TTJ, Sebastianelli A. Guideline No. 390-Classification and Management of Endometrial Hyperplasia. J Obstet Gynaecol Can. 2019; 41(12):1789-1800. https://doi.org/10.1016/j.jogc.2019.03.025. Erratum in: J Obstet Gynaecol Can. 2020; 42(10):1287.
Jewson M, Purohit P, Lumsden MA. Progesterone and abnormal uterine bleeding/ menstrual disorders. Best Pract Res Clin Obstet Gynaecol. 2020; 69:62-73. https://doi.org/10.1016/j.bpobgyn.2020.05.004.
Amezcua CA, Lu JJ, Felix JC, Stanczyk FZ, Zheng W. Apoptosis may be an early event of progestin therapy for endometrial hyperplasia. Gynecol Oncol. 2000; 79(2):169-176. https://doi.org/10.1006/gyno.2000.5955.
Abulafia O, Triest WE, Adcock JT, Sherer DM. The effect of medroxyprogesterone acetate on angiogenesis in complex endometrial hyperplasia. Gynecol Oncol. 1999;72(2):193-198. https://doi.org/10.1006/gyno.1998.5106.
Figueroa-Casas PR, Ettinger B, Delgado E, Javkin A, Vieder C. Reversal by medical treatment of endometrial hyperplasia caused by estrogen replacement therapy. Menopause. 2001; 8(6):420-423. https://doi.org/10.1097/00042192-200111000-00006.
Reed SD, Voigt LF, Newton KM, Garcia RH, Allison HK, Epplein M, et al. Progestin therapy of complex endometrial hyperplasia with and without atypia. Obstet Gynecol. 2009; 113(3):655-662. https://doi.org/10.1097/AOG.0b013e318198a10a.
Gunderson CC, Fader AN, Carson KA, Bristow RE. Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: a systematic review. Gynecol Oncol. 2012; 125(2):477-482. https://doi.org/10.1016/j.ygyno.2012.01.003.
Brun JL, Belaisch J, Rivel J, Hocké C. Les hyperplasies endométriales résistant aux progestatifs: alternatives aux traitements traditionnels. [Endometrial hyperplasias resistant to progestins: alternatives to traditional treatments]. Gynecol Obstet Fertil. 2002; 30(3):244-251. https://doi.org/10.1016/s1297-9589(02)00301-6.
Upson K, Allison KH, Reed SD, Jordan CD, Newton KM, Swisher EM, et al. Bio-markers of progestin therapy resistance and endometrial hyperplasia progression. Am J Obstet Gynecol. 2012; 207(1):36.e1-8. https://doi.org/10.1016/j.ajog.2012.05.012.
Wang S, Pudney J, Song J, Mor G, Schwartz PE, Zheng W. Mechanisms involved in the evolution of progestin resistance in human endometrial hyperplasia--precursor of endometrial cancer. Gynecol Oncol. 2003; 88(2):108-117. https://doi.org/10.1016/s0090-8258(02)00008-2.
Chen X, Zhang Z, Feng Y, Fadare O, Wang J, Ai Z, et al. Aberrant survivin expression in endometrial hyperplasia: another mechanism of progestin resistance. Mod Pathol. 2009; 22(5):699-708. https://doi.org/10.1038/modpathol.2009.25.
van Hylckama Vlieg A, Helmerhorst FM, Rosendaal FR. The risk of deep venous thrombosis associated with injectable depot-medroxyprogesterone acetate contraceptives or a levonorgestrel intrauterine device. Arterioscler Thromb Vasc Biol. 2010; 30(11):2297-2300. https://doi.org/10.1161/ATVBAHA.110.211482.
Vasilakis C, Jick H, del Mar Melero-Montes M. Risk of idiopathic venous thromboembolism in users of progestagens alone. Lancet. 1999; 354(9190):1610-1611. https://doi.org/10.1016/S0140-6736(99)04394-9.
Heinemann LA, Assmann A, DoMinh T, Garbe E. Oral progestogen-only contraceptives and cardiovascular risk: results from the Transnational Study on Oral Contraceptives and the Health of Young Women. Eur J Contracept Reprod Health Care. 1999; 4(2):67-73. https://doi.org/10.3109/13625189909064007.
Eichner E, Abellera M. Endometrial hyperplasia treated by progestins. Obstet Gynecol. 1971; 38 (5):739-42. PMID: 5114224.
Bese T, Vural A, Ozturk M, Dagistanli F, Demirkiran F, Tuncdemir M, et al. The effect of long-term use of progesterone therapy on proliferation and apoptosis in simple endometrial hyperplasia without atypia. Int J Gynecol Cancer. 2006; 16(2):809-813. https://doi.org/10.1111/j.1525-1438.2006.00533.x.
Buttini MJ, Jordan SJ, Webb PM. The effect of the levonorgestrel releasing intrauterine system on endometrial hyperplasia: An Australian study and systematic review. Aust N Z J Obstet Gynaecol. 2009; 49(3):316-322. https://doi.org/10.1111/j.1479-828X.2009.00981.x.
Ozdegirmenci O, Kayikcioglu F, Bozkurt U, Akgul MA, Haberal A. Comparison of the efficacy of three progestins in the treatment of simple endometrial hyperplasia without atypia. Gynecol Obstet Invest. 2011; 72(1):10-14. https://doi.org/10.1159/000321390.
Ushijima K, Yahata H, Yoshikawa H, Konishi I, Yasugi T, Saito T, et al. Multi-center phase II study of fertility-sparing treatment with medroxyprogesterone acetate for endometrial carcinoma and atypical hyperplasia in young women. J Clin Oncol. 2007; 25(19):2798-2803. https://doi.org/10.1200/JCO.2006.08.8344.
Güven M, Dikmen Y, Terek MC, Ozsaran AA, Itil IM, Erhan Y. Metabolic effects associated with high-dose continuous megestrol acetate administration in the treatment of endometrial pathology. Arch Gynecol Obstet. 2001; 265(4):183-186. https://doi.org/10.1007/s004040000154.
Gal D, Edman CD, Vellios F, Forney JP. Long-term effect of megestrol acetate in the treatment of endometrial hyperplasia. Am J Obstet Gynecol. 1983; 146(3):316-322. https://doi.org/10.1016/0002-9378(83)90754-8.
Garza-Flores J, Menjívar M, Cardenas M, Reynoso M, García GA, Pérez Palacios G. Further studies on the antigonadotropic mechanism of action of norethisterone. J Steroid Biochem Mol Biol. 1991; 38(1):89-93. https://doi.org/10.1016/0960-0760(91)90406-u.
Portman DJ, Symons JP, Wilborn W, Kempfert NJ. A randomized, double-blind, placebo-controlled, multicenter study that assessed the endometrial effects of norethindrone acetate plus ethinyl estradiol versus ethinyl estradiol alone. Am J Obstet Gynecol. 2003;188(2):334-342. https://doi.org/10.1067/mob.2003.91.
Nisker JA, Kirk ME, Nunez-Troconis JT. Reduced incidence of rabbit endometrial neoplasia with levonorgestrel implant. Am J Obstet Gynecol. 1988;158(2):300-303. https://doi.org/10.1016/0002-9378(88)90142-1.
Nilsson CG, Haukkamaa M, Vierola H, Luukkainen T. Tissue concentrations of levonorgestrel in women using a levonorgestrel-releasing IUD. Clin Endocrinol (Oxf). 1982; 17(6):529-536. https://doi.org/10.1111/j.1365-2265.1982.tb01625.x.
Suhonen SP, Allonen HO, Lähteenmäki P. Sustained-release estradiol implants and a levonorgestrel-releasing intrauterine device in hormone replacement therapy. Am Obstet Gynecol. 1995; 172(2 Pt 1):562-567. https://doi.org/10.1016/0002-9378(95)90573-1.
Abu Hashim H, Zayed A, Ghayaty E, El Rakhawy M. LNG-IUS treatment of non-atypical endometrial hyperplasia in perimenopausal women: a randomized controlled trial. J Gynecol Oncol. 2013; 24(2):128-134. https://doi.org/10.3802/jgo.2013.24.2.128.
Varma R, Soneja H, Bhatia K, Ganesan R, Rollason T, Clark TJ, Gupta JK. The effectiveness of a levonorgestrel-releasing intra-uterine system (LNG-IUS) in the treatment of endometrial hyperplasia a long-term follow-up study. Eur J Obstet Gynecol Re-prod Biol. 2008; 139(2):169-175. https://doi.org/10.1016/j.ejogrb.2008.02.022.
Vereide AB, Arnes M, Straume B, Maltau JM, Ørbo A. Nuclear morphometric changes and therapy monitoring in patients with endometrial hyperplasia: a study comparing effects of intrauterine levonorgestrel and systemic medroxyprogesterone. Gynecol Oncol. 2003; 91(3):526-533. https://doi.org/10.1016/j.ygyno.2003.07.002.
Singh G, Cue L, Puckett Y. Endometrial Hyperplasia. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.
The American College of Obstetricians and Gynecologists (ACOG). Management of Endometrial Intraepithelial Neoplasia or Atypical Endometrial Hyperplasia: ACOG Clinical Consensus No. 5. Obstet Gynecol. 2023; 142(3):735-744. https://doi.org/10.1097/AOG.0000000000005297.
Gallos ID, Shehmar M, Thangaratinam S, Papapostolou TK, Coomarasamy A, Gupta JK. Oral progestogens vs levonorgestrel releasing intrauterine system for endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol. 2010; 203(6):547.e1-10. https://doi.org/10.1016/j.ajog.2010.07.037.
Greenblatt RB, Dmowski WP, Mahesh VB, Scholer HF. Clinical studies with an antigonadotropin-Danazol. Fertil Steril. 1971; 22(2):102-112. https://doi.org/10.1016/s0015-0282(16)38045-1.
Crosignani P, Olive D, Bergqvist A, Luciano A. Advances in the management of endometriosis: an update for clinicians. Hum Reprod Update. 2006; 12(2):179-189. https://doi.org/10.1093/humupd/dmi049.
Mariani L, Sedati A, Giovinazzi R, Sindico R, Atlante G. Postmenopausal endome- trial hyperplasia: role of danazol therapy. Int J Gynaecol Obstet. 1994; 44(2):155-159. https://doi.org/10.1016/0020-7292(94)90071-x.
Soh E, Sato K. Clinical effects of danazol on endometrial hyperplasia in menopausal and postmenopausal women. Cancer. 1990; 66(5):983-988. https://doi.org/10.1002/1097-0142(19900901)66:5<983:aid-cncr2820660530>3.0.co;2-6.
Grio R, Piacentino R, Marchino GL, Bocci A, Navone R. Danazol in the treatment of endometrial hyperplasia. Panminerva Med. 1993; 35(4):231-233. PMID: 8202337.
Tamaoka Y, Orikasa H, Sumi Y, Sakakura K, Kamei K, Nagatani M, Ezawa S. Treatment of endometrial hyperplasia with a danazol-releasing intrauterine device: a prospective study. Gynecol Obstet Invest. 2004; 58(1):42-48. https://doi.org/10.1159/000077882.
Cottreau CM, Ness RB, Modugno F, Allen GO, Goodman MT. Endometriosis and its treatment with danazol or lupron in relation to ovarian cancer. Clin Cancer Res. 2003; 9(14):5142-5144. PMID: 14613992.
Vercellini P, Somigliana E, Viganò P, Abbiati A, Barbara G, Crosignani PG. Endometriosis: current therapies and new pharmacological developments. Drugs. 2009; 69(6):649-675. https://doi.org/10.2165/00003495-200969060-00002.
Akiyama T, Ishida J, Nakagawa S, Ogawara H, Watanabe S, Itoh N, et al. Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem. 1987; 262(12):5592-5595. PMID: 3106339.
Yamashita Y, Kawada S, Nakano H. Induction of mammalian topoisomerase II dependent DNA cleavage by nonintercalative flavonoids, genistein and orobol. Biochem Pharmacol. 1990; 39(4):737-744. https://doi.org/10.1016/0006-2952(90)90153-c.
Lian Z, Niwa K, Tagami K, Hashimoto M, Gao J, Yokoyama Y, Mori H, Tamaya T. Preventive effects of isoflavones, genistein and daidzein, on estradiol-17beta-related endometrial carcinogenesis in mice. J Cancer Res. 2001; 92(7):726-734. https://doi.org/10.1111/j.1349-7006.2001.tb01154.x.
Bitto A, Granese R, Triolo O, Villari D, Maisano D, Giordano D, et al. Genistein aglycone: a new therapeutic approach to reduce endometrial hyperplasia. Phytomedicine. 2010; 17(11):844-850. https://doi.org/10.1016/j.phymed.2010.03.024.
Núñez-Troconis, J. Uso de la metformina en el síndrome de ovarios poliquísticos. Gac Méd Caracas. 2021;129(1):128-139. https://doi.org/10.47307/GMC.2021.129.1.14
Shao R, Li X, Feng Y, Lin JF, Billig H. Direct effects of metformin in the endometrium: a hypothetical mechanism for the treatment of women with PCOS and endometrial carcinoma. J Exp Clin Cancer Res. 2014;33(1):41. https://doi.org/10.1186/1756-9966-33-41.
Núñez-Troconis, J. Uso de la metformina en cáncer ginecológico. Gac Méd Ca- racas 2021;129(1):88-106. https://doi.org/10.47307/GMC.2021.129.1.12.
Xie Y, Wang YL, Yu L, Hu Q, Ji L, Zhang Y, Liao QP. Metformin promotes progesterone receptor expression via inhibition of mammalian target of rapamycin (mTOR) in endometrial cancer cells. J Steroid Biochem Mol Biol. 2011; 126(3-5):113-120. https://doi.org/10.1016/j.jsbmb.2010.12.006.
Erdemoglu E, Güney M, Giray SG, Take G, Mungan T. Effects of metformin on mammalian target of rapamycin in a mouse model of endometrial hyperplasia. Eur J Obstet Gynecol Reprod Biol. 2009; 145(2):195-199. https://doi.org/10.1016/j.ejogrb.2009.04.034.
Session DR, Kalli KR, Tummon IS, Damario MA, Dumesic DA. Treatment of atypical endometrial hyperplasia with an insulin-sensitizing agent. Gynecol Endocrinol. 2003; 17(5):405-407. https://doi.org/10.1080/09513590312331290298.
Shen ZQ, Zhu HT, Lin JF. Reverse of progestin-resistant atypical endometrial hyperplasia by metformin and oral contraceptives. Obstet Gynecol. 2008;112(2 Pt 2):465-467. https://doi.org/10.1097/AOG.0b013e3181719b92.
Meresman GF, Bilotas MA, Lombardi E, Tesone M, Sueldo C, Barañao RI. Effect of GnRH analogues on apoptosis and release of interleukin-1beta and vascular endothelial growth factor in endometrial cell cultures from patients with endometriosis. Hum Reprod. 2003; 18(9):1767-1771. https://doi.org/10.1093/humrep/deg356.
Fister S, Günthert AR, Emons G, Gründker C. Gonadotropin-releasing hormone type II antagonists induce apoptotic cell death in human endometrial and ovarian cancer cells in vitro and in vivo. Cancer Res. 2007; 67(4):1750-1756. https://doi.org/10.1158/0008-5472.CAN-06-3222.
Agorastos T, Bontis J, Vakiani A, Vavilis D, Constantinidis T. Treatment of endometrial hyperplasias with gonadotropin-releasing hormone agonists: pathological, clinical, morphometric, and DNA-cytometric data. Gynecol Oncol. 1997; 65(1):102-114. https://doi.org/10.1006/gyno.1997.4639.
Agorastos T, Vaitsi V, Paschopoulos M, Vakiani A, Zournatzi-Koiou V, Saravelos H, et al. Prolonged use of gonadotropin releasing hormone agonist and tibolone as add-back therapy for the treatment of endometrial hyperplasia. Maturitas. 2004;48(2):125-132. https://doi.org/10.1016/j.maturitas.2003.08.008.
Yu K, Huang ZY, Xu XL, Li J, Fu XW, Deng SL. Estrogen Receptor Function: Impact on the Human Endometrium. Front Endocrinol (Lausanne). 2022; 13:827724. https://doi.org/10.3389/fendo.2022.827724.
Long BJ, Tilghman SL, Yue W, Thiantanawat A, Grigoryev DN, Brodie AM. The steroidal antiestrogen ICI 182,780 is an inhibitor of cellular aromatase activity. J Steroid Biochem Mol Biol. 1998; 67(4):293-304. https://doi.org/10.1016/s0960-0760(98)00122-8.
Scott SM, Brown M, Come SE. Emerging data on the efficacy and safety of Fulvestrant, a unique antiestrogen therapy for advanced breast cancer. Expert Opin Drug Saf. 2011; 10(5):819-826. https://doi.org/10.1517/14740338.2011.595560.
Sourla A, Luo S, Labrie C, Bélanger A, Labrie F. Morphological changes induced by 6-month treatment of intact and ovariectomized mice with tamoxifen and the pure antiestrogen EM-800. Endocrinology. 1997; 138(12):5605-5617. https://doi.org/10.1210/endo.138.12.5560.
Tremblay A, Tremblay GB, Labrie C, Labrie F, Giguère V. EM-800, a novel antiestrogen, acts as a pure antagonist of the transcriptional functions of estrogen receptors alpha and beta. Endocrinology. 1998; 139(1):111-118. https://doi.org/10.1210/endo.139.1.5702.
Fatima I, Chandra V, Saxena R, Manohar M, Sanghani Y, Hajela K, et al. 2,3-Diaryl-2H-1-benzopyran derivatives interfere with classical and non-classical estrogen receptor signaling pathways, inhibit Akt activation and induce apoptosis in human endometrial cancer cells. Mol Cell Endocrinol. 2012; 348(1):198-210. https://doi.org/10.1016/j.mce.2011.08.018.
Chandra V, Fatima I, Saxena R, Kitchlu S, Sharma S, Hussain MK, et al. Apoptosis induction and inhibition of hyperplasia formation by 2-[piperidinoethoxyphenyl]- 3-[4-hydroxyphenyl]-2H-benzo(b)pyran in rat uterus. Am J Obstet Gynecol. 2011; 205(4):362.e1-11. https://doi.org/10.1016/j.ajog.2011.05.024. Erratum in: Am J Obstet Gynecol. 2020; 222(1):84.
Chandra V, Fatima I, Manohar M, Popli P, Sirohi VK, Hussain MK, et al. Inhibitory effect of 2-(piperidinoethoxyphenyl)-3-(4-hydroxyphenyl)-2H-benzo(b)pyran (K-1) on human primary endometrial hyperplasial cells mediated via combined suppression of Wnt/β-catenin signaling and PI3K/ Akt survival pathway. Cell Death Dis. 2014; 5(8):e1380. https://doi.org/10.1038/cddis.2014.334.
Fabian CJ. The what, why and how of aromatase inhibitors: hormonal agents for treatment and prevention of breast cancer. Int J Clin Pract. 2007; 61(12):2051- 2063. https://doi.org/10.1111/j.1742-1241.2007.01587.x.
Bershteĭn LM, Maksimov SIa, Danilova MA, Gershfel’d ÉD, Boiarkina MP, Khadzhimba AS, et al. [Effectiveness of aromatase inhibitors in comparison with metformin for neoadjuvant treatment in patients with endometrial cancer]. Vopr Onkol. 2011; 57(6):737-741. Russian.PMID: 22416390.
Lai CH, Huang HJ. The role of hormones for the treatment of endometrial hyperplasia and endometrial cancer. Curr Opin Obstet Gynecol. 2006; 18(1):29-34. https://doi.org/10.1097/01.gco.0000192994.37965.c6.
Barker LC, Brand IR, Crawford SM. Sustained effect of the aromatase inhibitors anastrozole and letrozole on endometrial thickness in patients with endometrial hyperplasia and endometrial carcinoma. Curr Med Res Opin. 2009; 25(5):1105-1109. https://doi.org/10.1185/03007990902860549.
Tabatabaie A, Karimi Zarchi M, Dehghani-Tafti M, Miratashi-Yazdi A, Teimoori S, Dehghani A. Comparing letrozole with medroxyprogesterone acetate (MPA) as hormonal therapy for simple endometrial hyperplasia without atypia in adult and middle-aged women. Eur J Gynaecol Oncol. 2013; 34(6):552-555. PMID:24601050.
El-shamy M, Gibreel A, Refai E, Sadek E, Ragab A. Aromatase inhibitor “letrozole” versus progestin “norethisterone” in women with simple endometrial hyperplasia without atypia: a prospective co-hort trial. Middle East Fertil Soc J. 2012; 17(2):111-115. https://doi.org/10.1016/j.mefs.2011.11.005.
Agorastos T, Vaitsi V, Pantazis K, Efstathiadis E, Vavilis D, Bontis JN. Aromatase inhibitor anastrozole for treating endometrial hyperplasia in obese postmenopausal women. Eur J Obstet Gynecol Re-prod Biol. 2005; 118(2):239-240. https://doi.org/10.1016/j.ejogrb.2004.07.002.
Guo Y, Chen Y, Liu LB, Chang KK, Li H, Li MQ, Shao J. IL -22 in the endometriotic milieu promotes the proliferation of endometrial stromal cells via stimulating the secretion of CCL2 and IL-8. Int J Clin Exp Pathol. 2013; 6(10):2011-2020. PMID:2133578.
Bruchim I, Sarfstein R, Werner H. The IGF Hormonal Network in Endometrial Cancer: Functions, Regulation, and Targeting Approaches. Front Endocrinol (Lausanne). 2014; 5:76. https://doi.org/10.3389/fendo.2014.00076.
Li MQ, Li HP, Meng YH, Wang XQ, Zhu XY, Mei J, Li DJ. Chemokine CCL2 enhances survival and invasiveness of endometrial stromal cells in an autocrine manner by activating Akt and MAPK/Erk1/2 signal pathway. Fertil Steril. 2012; 97(4):919-929. https://doi.org/10.1016/j.fertnstert.2011.12.049.
Del Priore G, Gudipudi DK, Montemarano N, Restivo AM, Malanowska-Stega J, Arslan AA. Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia. Gynecol Oncol. 2010;116(3):464-467. https://doi.org/10.1016/j.ygyno.2009.10.060.
Dalessandri KM, Firestone GL, Fitch MD, Bradlow HL, Bjeldanes LF. Pilot study: effect of 3,3’-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutr Cancer. 2004;50(2):161-167. https://doi.org/10.1207/s15327914nc5002_5.
Chen DZ, Qi M, Auborn KJ, Carter TH. Indole-3-carbinol and diindolylmethane induce apoptosis of human cervical cancer cells and in murine HPV16-transgenic preneoplastic cervical epithelium. J Nutr. 2001;131(12):3294-3302. https://doi.org/10.1093/jn/131.12.3294.
Savino JA 3rd, Evans JF, Rabinowitz D, Auborn KJ, Carter TH. Multiple, disparate roles for calcium signaling in apoptosis of human prostate and cervical cancer cells exposed to diindolylmethane. Mol Cancer Ther. 2006;5(3):556-563. https://doi.org/10.1158/1535-7163.MCT-05-0355.
Leong H, Firestone GL, Bjeldanes LF. Cytostatic effects of 3,3′-diindolylmethane in human endometrial cancer cells result from an estrogen receptor-mediated increase in transforming growth factor-α expression. Carcinogenesis. 2001; 22(11):1809-1817. https://doi.org/10.1093/carcin/22.11.1809.
Järvelä I, Tekay A, Santala M, Jouppila P. Thermal balloon endometrial ablation therapy induces a rise in uterine blood flow impedance: a randomized prospective color Doppler study. Ultrasound Obstet Gynecol. 2001;17(1):65-70. https://doi.org/10.1046/j.1469-0705.2001.00317.
Publicado
2025-12-08
Cómo citar
Núñez-Troconis, J. (2025). Hiperplasia endometrial II: Revisión narrativa sobre diferentes opciones de tratamiento.: Endometrial hyperplasia II: A narrative review of different treatment options. Investigación Clínica, 66(4), 436-453. https://doi.org/10.54817/IC.v66n4a07
Sección
Revisiones
